Augmentation of antibacterial activity of ciprofloxacin by bisabololoxide A encapsulated in polymeric nanoparticles against uropathogenic Escherichia coli
Abstract
BACKGROUND: Multidrug-resistant uropathogenic Escherichia coli (UPEC) are a major cause of urinary tract infections, largely due to efflux pump overexpression, porin alterations, and increasing biofilm formation. To address these challenges, we developed bisabololoxide A-loaded PEG400-oleate polymeric nanoparticles (BAPNs) and evaluated their potential to enhance the efficacy of ciprofloxacin against ciprofloxacin-resistant isolates. MATERIALS AND METHODS: BAPNs were synthesized and characterized by FTIR, TEM, FE-SEM, EDX, TGA, and zeta potential analysis. The synergistic effects of BAPNs and ciprofloxacin were evaluated in drug-resistant isolates. The inhibition of Biofilm formationwas quantified by crystal violet staining and gene expression changes in some genes related to efflux pumps, porins and biofilm formation were analyzed in two representative isolates by qPCR. RESULTS: BAPNs exhibited a spherical morphology with sizes ranging from 17 to 28 nm (TEM) and 30–43 nm (FE-SEM). Checkerboard analysis showed that the MIC of ciprofloxacin decreased by 2- to 32-fold in ciprofloxacin-resistant isolates and the ATCC 8739 strain when combined with BAPNs. Biofilm inhibition was significantly enhanced with the combined therapy compared to ciprofloxacin alone. qPCR analysis further revealed significant downregulation of the AcrAB-TolC efflux pump genes and the virulence genes fimH and hlyA, along with upregulation of the porin genes (ompC and ompF). Furthermore, molecular docking…
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